5-Oxa phenyl- and phenoxy-substituted prostaglandin β, analogs

ABSTRACT

5-Oxa phenyl- and phenoxy-substituted prostaglandin-β 1  type compounds and processes for making them. These compounds are useful for a variety of pharmacological purposes, including stimulation of epidermal proliferation and keratinization, and wound healing.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of my co-pending application Ser. No. 361,990 filed May 21, 1973 now issued as U.S. Pat. No. 3,864,387.

BACKGROUND OF THE INVENTION

This invention relates to novel compositions of matter, to novel methods for producing those, and to novel chemical intermediates useful in those processes. Particularly, this invention relates to certain novel analogs of prostaglandins E₁, F₁.sub.α, F₁.sub.β, A₁, and B₁ in which the C-5 methylene (--CH₂) in the prostanoic acid structure is replaced by oxygen (--O--).

The essential material for this application, including the background of the invention, the disclosure of the invention, and the description of the preferred embodiments, including Preparations and Examples, is incorporated by reference from U.S. Pat. No. 3,864,387, columns 1-89 inclusive, under the provisions of M.P.E.P. 608.01(p). 

I claim:
 1. An optically active compound of the formula ##EQU1##or a racemic compound of that formula and the mirror image thereof, wherein Z represents an oxa atom (--O--) or C_(j) H₂ j wherein C_(j) H₂ j is a valence bond or alkylene of 1 to 9 carbon atoms, inclusive, substituted with 0, 1, or 2 fluoro, with one to 6 carbon atoms, inclusive, between --CR₈ R₉ -- and the ring; wherein T is alkyl of 1 to 4 carbon atoms, inclusive, fluoro, chloro, trifluoromethyl, or --OR₁₀, wherein R₁₀ is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, and s is 0, 1, 2, or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 the T's are either the same or different; wherein Q₁ is ##EQU2## wherein R₆ and R₇ are hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, being the same or different; wherein R₁ is hydrogen, alkyl) of 1 to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, or phenyl substituted with 1, 2, or 3 chloro or alkyl of one to 4 carbon atoms, inclusive; wherein when Z is oxa (--O--), R₈ and R₉ are hydrogen or alkyl of one to 4 carbon atoms, being the same or different, and, when Z is C_(j) H_(2j), R₈ and R₉ are hydrogen, alkyl of 1 to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that R₉ is fluoro only when R₈ is hydrogen or fluoro; wherein R₃ is hydrogen, alkyl of 1 to 4 carbon atoms, inclusive, or fluoro; wherein R₂ is hydrogen or fluoro, with the proviso that R₂ is fluoro only when R₃ is hydrogen or fluoro; and wherein R₄ and R₅ are hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, being the same or different, with the proviso that no more than one of R₃, R₄, and R₅ is alkyl; including the lower alkanoates thereof, and the pharmacologically acceptables salts thereof when R₁ is hydrogen.
 2. A compound according to claim 1 wherein Q₁ is ##EQU3## wherein R₆ and R₇ are hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, being the same or different.
 3. A compound according to claim 2 wherein R₂, R₃, R₄, and R₅ are hydrogen.
 4. A compound according to claim 3 wherein R₆, R₇, R₈, and R₉ are either hydrogen or methyl, and one of R₆, R₇, R₈, and R₉ is methyl.
 5. A compound according to claim 3 wherein R₆, R₇, R₈, and R₉ are hydrogen.
 6. A compound according to claim 5 wherein Z is oxa (--O--).
 7. A compound according to claim 5 wherein Z is methylene.
 8. A compound according to claim 7 wherein R₁ is alkyl of 1 to 12 carbon atoms, inclusive.
 9. 5-Oxa-17-phenyl-18,19,20-trinor-PGB₁, methyl ester, a compound according to claim
 8. 10. A compound according to claim 7 wherein R₁ is hydrogen. 